Abstract

The present study reports the comparative effects of pimozide (PMZ; 0.1, 0.3 and 1.0 mg/kg) and clozapine (CZP; 1.0, 3.0 and 10.0 mg/kg) on fixed-interval 60-sec responding after acute and chronic administration and on the acquisition of schedule-induced drinking (SID) during a chronic dosing procedure. Both the 0.3 and the 1.0 mg/kg of PMZ groups responded significantly less than vehicle controls after acute dosing without disrupting the operant response patterns as measured by index of curvature (IOC), and these effects persisted for 38 days of treatment. Acute treatment with 3.0 and 10.0 mg/kg of CZP significantly suppressed operant response rates and disrupted the pattern of operant responding, in that the IOC was significantly lower for these subjects than for vehicle controls. The CZP-treated animals gradually developed tolerance to the drug effects and were performing at vehicle control levels after Day 7 of treatment. SID was assessed from Day 19 through Day 38 of neuroleptic treatment. PMZ suppressed the acquisition of SID. Animals treated with 1.0 and 0.3 mg/kg of PMZ consumed less water than controls and did not develop the postpellet drinking pattern characteristic of SID. Both the vehicle and 0.1 mg/kg of PMZ groups increased the amount of water they consumed across the 10 blocks of sessions. A dose-related suppression of SID also was noted for CZP-treated rats. Vehicle controls and three of the subjects treated with 10.0 mg/kg of CZP acquired the SID behavior. These animals gradually increased the amount of water they consumed across sessions and drank in a temporal pattern consistent with SID.(ABSTRACT TRUNCATED AT 250 WORDS)